Smooth muscle cells (SMC's) are heterogeneous in their myosin isoform expression. The evidence that this correlates with their contractile function is critical for further understanding their function and dysfunction in normal and pathological states. For example, the vascular disease atherosclerosis is the major cause of morbidity and mortality in humans. It involves a thickening of the intimal layer by, in part, a proliferation of SMC's. Unfortunately, little is know about the myosin isoform expression and mechanical properties of medial SMC's, and virtually nothing is known of the intimal SMC's. We propose investigating the myosin isoform expression and mechanics of single SMCs and SM tissues under normal and experimentally induced pathological conditions. The results will increase our understanding of the biology of the SMC and the molecular basis for the differences in phenotype of the medial and intimal SMCs. The specific aims of this grant are to test the hypotheses that: 1) SM1/2 MHC tail isoforms but not the SMA/B MHC head or MLC17a/b isoforms correlate with force production. 2) MHC isoforms show differential distribution between and within cells from a given tissue. 3) In contrast to the classical striated muscle length-tension relationship with a unique optimal length (Lo), SMC's can shift (alter) their Lo by varying the organization of contractile units to adapt to different cell lengths. 4) SMC's found in the intimal thickening of an atherosclerotic vessel will differ in their myosin isoform expression and mechanical properties relative to the medial SMC's. [unreadable] [unreadable]